Whereas protection following natural infection with systemic viruses (such as measles, mumps, rubella, or varicella) is usually life-long and complete (1), protection following infection with mucosal viruses (such as rotavirus, influenza virus or respiratory syncytial virus) is usually short-lived and incomplete (2). Two observations might explain these differences. First, antibody-secreting cells (ASC) at mucosal surfaces after natural infection or immunization (primary ASC) are short-lived (3). Second, the time required for generation of secondary ASC derived from memory B cells is often longer than the incubation periods of most mucosal pathogens. Therefore, development of vaccines that provide long-lived and complete protection against mucosal pathogens will depend upon either prolonging primary ASC after immunization or hastening the onset of secondary ASC after challenge. To enhance virus-specific mucosal immune responses, we recently developed a system of microencapsulation based on the ionic linkage of aqueous polymers and aqueous amines (10). We found that microcapsules enhance the magnitude of primary and secondary rotavirus-specific ASC and enhance protection against rotavirus challenge. Although the mechanism by which microcapsules enhance protective virus-specific immune responses remains unclear, we found that microcapsules containing rotavirus might select for antigen-presenting cells (APC) different from and perhaps more efficient that those involved during natural infection. Using microencapsulated and unencapsulated preparations of rotavirus, we will determine whether APC type (i.e. dendritic cells, macrophages, B cells, or intestinal epithelial cells) alters primary or secondary ASC responses. In addition, by biologically or chemically modifying microcapsules, we will determine whether alteration in the type of APC recruited during mucosal infection, or alteration in the kinetics of antigen presentation, modifies protective immune responses. The availability of microencapsulated virus provides a unique opportunity to understand the relationship between APC and protective mucosal immune responses.